BACKGROUND The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors for progression may differ from those for men. OBJECTIVE The objective was to investigate associations between dietary macronutrients and progression of coronary atherosclerosis among postmenopausal women. METHODS Quantitative coronary angiography was performed at baseline and after a mean follow-up of 3.1 y in 2243 coronary segments in 235 postmenopausal women with established coronary heart disease. Usual dietary intake was assessed at baseline. RESULTS The mean (+/-SD) total fat intake was 25 +/- 6% of energy. In multivariate analyses, a higher saturated fat intake was associated with a smaller decline in mean minimal coronary diameter (P = 0.001) and less progression of coronary stenosis (P = 0.002) during follow-up. Compared with a 0.22-mm decline in the lowest quartile of intake, there was a 0.10-mm decline in the second quartile (P = 0.002), a 0.07-mm decline in the third quartile (P = 0.002), and no decline in the fourth quartile (P < 0.001); P for trend = 0.001. This inverse association was more pronounced among women with lower monounsaturated fat (P for interaction = 0.04) and higher carbohydrate (P for interaction = 0.004) intakes and possibly lower total fat intake (P for interaction = 0.09). Carbohydrate intake was positively associated with atherosclerotic progression (P = 0.001), particularly when the glycemic index was high. Polyunsaturated fat intake was positively associated with progression when replacing other fats (P = 0.04) but not when replacing carbohydrate or protein. Monounsaturated and total fat intakes were not associated with progression. CONCLUSIONS In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with less progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a greater progression.